Blood Cancer Drug Decitabine May Prevent Breast Cancer Metastasis

In In The News by Barbara Jacoby

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Breast tumors can shed cells, but if Decitabine, a drug now used to treat lymphoma and leukemia, is approved for use in breast cancer, it could prevent the metastasis of most forms of this disease.

Dr. Peter Storz, of the Mayo Clinic, led a research study that concluded that protein kinase D (PKD) expression in breast tissue and breast tumors could be used as a marker for invasive breast cancer. A kinase called PKD1 was found to inhibit the shedding of breast cancer cells – an important function that could stop the spread of invasive types of breast cancer. But when a tumor produced Matrix metalloproteinases (MMPs), those substances could turn off the protective action of PKD1 kinase. The researchers looked for a way to reactivate the PKD1 and let it resume its job of stopping cancer cells from shedding. In lab studies on human breast tissue and on rabbits, small doses of decitabine were able to activate PKD1, shrink the tumor, and prevent the spread of cancer. This therapy worked on all types of breast cancer, with the exception of invasive lobular carcinoma.

Decitabine acts by turning on the gene code for PKD1. This protein kinase D will stop the spread of breast cancer from the tumor to the bloodstream and thus to organs such as lungs, bones, brain, and other distant organs. When breast cancer spreads to distant sites from the primary tumor, it is at Stage 4, and much more difficult to treat. If a test for silenced PKD1 is developed, then future breast cancer patients may benefit. Their tumor tissue would be examined for PKD1 expression, and if it isn’t working, then decitabine could be added to the treatment regimen to help fight the cancer.

“Because we found that PRKD1 is increasingly silenced as breast cancer becomes aggressive and spreads, the hope is that this test can be further developed and used to predict which patients are at risk for cancer metastasis, and thus may benefit from decitabine,” said Dr Sahra Borges, the team member who is working on the genetic assay for PRKD1 expression.